Chronic high dose of captopril induces depressive-like behaviors in mice: possible mechanism of regulatory T cell in depression

Abstract

Major depression has various types of symptoms and disease courses with inconsistent response to monoamine-related antidepressants. Thus, monoamine theory may not be the only pathophysiologic pathway relevant to depression. Recently, it has been suggested that regulatory T cell (Treg) is associated with depression. Based on our previous study that showed decreased regulatory T cell (Treg) population following chronic high-dose captopril (CHC, 40 mg/kg/day * 21 days) administration, we examined whether CHC alone can induce depressive-like behaviors in mice even without stressful stimuli. In this study, we found that CHC induced depressive-like behaviors in tail suspension test (TST) and forced swimming test (FST) without systemic illness, while it did not induce anhedonic behavior, anxiety-like behaviors, or sociality-related behavior. The depressive-like behaviors were rescued by either CHC washout or antidepressant. CHC caused reduction in foxp3 and gata3 mRNA expression in the lymph nodes with elevation in plasma IL-1β and IL-6. Interestingly, CHC increased serum angiotensin II level. In the hippocampus, CHC increased TNF-α and IL-6 mRNA expression with microglia activation while reduced glucocorticoid receptor expression. However, CHC did not affect to hippocampal kynurenine pathway, serotonin level, hypothalamic corticotropin-releasing hormone mRNA level, or serum corticosterone level. Consequently, we propose that CHC may induce a specific form of depressive-like behaviors via Treg reduction and microglial activation.

SGK1-FoxO1 Signaling Pathway Mediates Th17/Treg Imbalance and Target Organ Inflammation in Angiotensin II-Induced Hypertension

“…Furthermore, the present study demonstrated that SGK1 inhibitor EMD638683 significantly inhibited the increased peripheral cytokines in AngII-induced hypertensive mice. This finding is consistent with previous studies showing that peripheral cytokines such as IL-17, IL-6, IL-1β, Interferonγ (IFN-γ), monocyte chemoattractant protein 1 (MCP-1), vascular endothelial growth factor (VEGF), and TNF-α were increased and contributed to target organ damages in AngII-induced hypertension in mice ( Lee et al, 2006 ; Sanchez-Lemus et al, 2009 ; Madhur et al, 2010 ; Mirhafez et al, 2014 ; Park et al, 2017 ). For example, it has been shown that IL-17 production from T cells and IL-17 protein in the aortic media, and that the IL-17 deficiency displayed preserved vascular function, decreased superoxide production, and reduced T-cell infiltration in response to angiotensin II ( Madhur et al, 2010 ).…”

Chronically infused angiotensin II induces depressive-like behavior via microglia activation

“…Behavioral testing. Behavior testing was performed according to our previous studies 26 www.nature.com/scientificreports/ www.nature.com/scientificreports/ Figure 7. Schematic representation of ANGII-induced depressive-like behaviors.…”

Role of Corticotropin Releasing Factor in the Neuroimmune Mechanisms of Depression: Examination of Current Pharmaceutical and Herbal Therapies

“…However, a recent study reported that chronic high-dose captopril (CHC) administration can induce a specific form of depressive-like behavior. This effect is caused by Treg reduction and microglial activation with unaltered CRF levels and HPA axis activity (Park et al, 2017). This finding suggests that the activation of immune cells as a response to depression can also be independent of CRF and the HPA axis regulation.…”